Deep brain stimulation (DBS) is currently under investigation for treatment of a number of psychiatric indications, including obsessive–compulsive disorder, treatment-resistant depression, and Tourette’s syndrome. Despite its clinical efficacy, the mechanism of action of DBS is incompletely understood. Contrary to the previously proposed mechanism of local inhibition of neural elements at the stimulation site, recent studies have argued that DBS may also cause excitation of efferent target neurons and subsequent changes in neural network activity and neurotransmitter release at various nodes within the neural network. However, the necessary link between symptom change and a corresponding change in neurotransmitters has yet to be firmly established and will be essential to advance our understanding of psychiatric neurobiology. In this chapter, we briefly review the growing scientific evidence in regard to neurotransmitter release as a possible mechanism of action of DBS and the potential impact on neuropsychiatric applications.
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